Pipetting device

ABSTRACT

The invention relates to a pipetting device ( 1 ) for an automatic analysis appliance, wherein the pipetting device ( 1 ) comprises a pipetting needle ( 2 ) with a longitudinal axis ( 3 ), and a device ( 4 ) for moving the pipetting needle ( 2 ). The pipetting device ( 1 ) further comprises a holder ( 5 ) for the pipetting needle ( 2 ), which holder ( 5 ) is mounted on the movable device ( 4 ) and to which holder the pipetting needle ( 2 ) is releasably connected, and a vibration generator which can set at least the tip of the pipetting needle ( 2 ) in vibration, wherein the vibration generator is mounted on the movable device ( 4 ).

CROSS REFERENCE TO RELATED APPLICATION

This claims priority to European Patent Application No. EP 15168487.5,filed May 20, 2015, which is hereby incorporated by reference herein inits entirety for all purposes.

FIELD

The invention relates to a pipetting device for an automatic analyzerand concerns the technical field of automatic in vitro diagnosticsystems.

BACKGROUND

Nowadays, many detection and analysis methods for determiningphysiological parameters in samples of body fluids or in otherbiological samples are carried out in an automated manner and in largenumbers in automatic analysis appliances or so-called in vitrodiagnostics systems.

Today's analysis appliances are able to carry out a large number ofdetection reactions and analyses with one sample. To be able to carryout a large number of tests in an automated manner, various devices areneeded for the spatial transfer of measurement cells, reactioncontainers and reagent containers, e.g., transfer arms with a grippingfunction, transport belts or rotatable transport wheels, and devices fortransfer of liquids, e.g., pipetting devices. The appliances comprise acontrol unit which, by means of suitable software, is able, largelyindependently, to plan and work out the work steps for the desiredanalyses.

Many of the analysis methods used in such automated analysis appliancesare based on optical techniques. These methods permit the qualitativeand quantitative detection of analytes, i.e., the substances to bedetected or to be determined, in samples. Clinically relevantparameters, such as the concentration or activity of an analyte, areoften determined by means of a portion of a sample being mixed with oneor more test reagents in a reaction vessel, which can also be themeasurement cell, as a result of which, for example, a biochemicalreaction or a specific binding reaction is started which brings about ameasurable change in an optical or other physical property of the testmixture.

It is known that, in automatic analyzers used to test biological bodyfluids, the required reagents are introduced into a measurement cuvetteby means of a pipetting device with a pipetting needle. The pipettingdevice additionally has the role of ensuring that the body fluid to betested is thoroughly mixed with the reagents. For this purpose, it isnecessary to set the pipetting needle in vibration. Hitherto, it waspossible to set the pipetting needle in vibration only at defined,stationary positions in an automatic analyzer where vibration generatorswhich cannot be moved are provided (see, for example, EP 0994356 A2).This has the effect that the sample cannot be thoroughly mixed at allpositions to which the pipetting needle can be driven. Moreover,thorough mixing of the sample is in principle not possible during atransfer of the pipetting needle from a first position in the analysisappliance to a second position in the analysis appliance. This has theeffect of taking up more time and considerably reduces the flexibilityin the execution of an analysis in an automatic analysis appliance.

SUMMARY

The object of the invention is therefore to make available a pipettingdevice which reduces the time taken and permits a greater degree offlexibility in the performance of an analysis in an automatic analysisappliance.

It has been found that an improved pipetting device can be achieved ifthe vibration generator is mounted on the movable device for moving thepipetting needle.

This has the advantage that the pipetting needle can be set in vibrationat every position, and therefore a sample can be thoroughly mixedindependently of fixed positions of the pipetting needle. Moreover,mixing is also possible during a transfer of the pipetting needle from afirst position in the analysis appliance to a second position in theanalysis appliance. This permits, for example, a reduction in terms oftime and an increased flexibility in the execution of an analysis in anautomatic analysis appliance.

The subject of the present invention is a pipetting device for anautomatic analysis appliance wherein the pipetting device comprises apipetting needle with a longitudinal axis for the pipetting of liquids,a device which is movable in the direction of the longitudinal axis ofthe pipetting needle and in at least one direction perpendicular to thedirection of the longitudinal axis of the pipetting needle and which isused for moving the pipetting needle. Moreover, the pipetting devicecomprises a holder for the pipetting needle, which holder is mounted onthe movable device and to which holder the pipetting needle isreleasably connected, and a vibration generator which can set at leastthe tip of the pipetting needle in vibration. The vibration generator ismounted on the movable device or on the holder for the pipetting needle.

The movable device is preferably designed as an automatically movablerobot arm which, for example, is part of an automatic robot station.

In a particularly preferred embodiment, the pipetting device comprises amovable first connection element with a first resetting element, whereinthe first connection element produces a releasable connection betweenthe pipetting needle and the vibration generator. The first connectionelement is preferably movable relative to the pipetting needle in thedirection of the longitudinal axis of the pipetting needle. This has theadvantage that the releasable connection between the pipetting needleand the vibration generator can be produced and separated in aparticularly simple and cost-effective manner. In the operating state ofthe pipetting device, the pipetting needle is inserted into the holderand the vibration generator is connected to the pipetting needle via thefirst connection element, such that the vibration generator is able toset the tip of the pipetting needle in vibration. The first resettingelement exerts a restoring force on the first connection element, whichforce keeps the first connection element in a position in which thefirst connection element produces a connection between the pipettingneedle and the vibration generator when the pipetting needle is insertedin the holder.

Preferably, the first connection element has the shape of an anglepiece. The angle piece preferably has two limbs which are arranged atright angles to each other. The angle piece is preferably made of metalor plastic. This has the advantage that the releasable connectionbetween the pipetting needle and the vibration generator can be producedand separated in a particularly simple and cost-effective manner.Advantageously, the first connection element in this case has a recessin which an eccentric, which is part of the vibration generator, canengage.

In an advantageous embodiment, the pipetting device comprises a firstand a second securing element, wherein the pipetting needle comprises asuspension, and wherein the first securing element is mounted laterallyon the suspension and is designed as a blade, and wherein the secondsecuring element is mounted on the holder and is designed as a prismbearing. This has the advantage that the needle according to theinvention can be replaced in a way that is particularly easy anduncomplicated. Moreover, this has the advantage that the pipettingneedle can be inserted, in particular repeatedly, in a precisely definedposition.

In a preferred embodiment, a clamping screw is provided which is able tofix the first connection element in a position. In the operating stateof the pipetting device, the clamping screw preferably fixes the firstconnection element in a position in which the first connection elementproduces a connection between the pipetting needle and the vibrationgenerator when the pipetting needle is inserted into the holder. Theclamping screw is preferably secured on the suspension of the pipettingneedle.

When the reagents are being introduced, and during the subsequentactions, there is the danger of the sensitive pipetting needle collidingwith the measurement cuvette or other appliance parts, being damaged asa result, and having to be replaced because it is unusable. Inconventional systems, replacement of the pipetting needle often entailsconsiderable technical knowhow, which can be provided only by aspecially trained maintenance technician. For example, it is not justthe pipetting needle itself and other mechanical parts that have to bereplaced, but also the motor and the eccentric bearing. This involvesquite considerable expenditure in terms of time and/or cost. It istherefore also of particular importance from an economic point of viewthat the needle according to the invention can be replaced in a way thatis particularly easy and uncomplicated, since this allows the operatingpersonnel working on the analyzer to replace a damaged pipetting needlequickly and easily without calling on the assistance of a speciallytrained technician.

In another advantageous embodiment, the pipetting device comprises asecond resetting element, wherein the second resetting element can fixthe blade and the prism bearing in a stable position and releasablyconnect them. This has the advantage that the pipetting needle can befixed repeatedly in a precisely defined position, and a releasableconnection between the blade and the prism bearing is easy to produceand to release.

The second resetting element is preferably a spring element,particularly preferably a leaf spring. This has the advantage that theresetting element can be produced particularly easily andcost-effectively.

In an advantageous embodiment, the vibration generator comprises aneccentrically rotating shaft, which can engage in a recess of the firstconnection element. This has the advantage that the connection betweenthe vibration generator and the pipetting needle is particularly easy toproduce and to release. Moreover, this has the advantage that thetransmission of vibrations from the vibration generator to the pipettingneedle by means of the first connection element is possible in aparticularly simple way.

The eccentrically rotating shaft can be an eccentric shaft, for example.

Advantageously, the eccentric bearing comprises at least one ballbearing. The contact between the eccentrically rotating shaft and theedge of the recess of the first connection element, in which theeccentrically rotating shaft at least partially engages, is preferablyproduced by means of the ball bearing. This ball bearing is alsoreferred to as the eccentric ball bearing. This has the advantage thatwear of the eccentric ball bearing or of the edge of the recess of thefirst connection element is minimized. Moreover, any frictional forcesthat arise are minimized.

A first sensor is preferably provided which detects the position of theeccentrically rotating shaft. This has the advantage of being able toensure that the pipetting needle is located in the vertical position, orwithin a defined deviation from the vertical position, after a shakingprocess. Precise positioning of the pipetting needle is therebypossible. This also avoids a situation in which the eccentricallyrotating shaft of the vibration generator happens to come to astandstill in a position in which the pipetting needle does not liesufficiently perpendicularly and in which precise positioning of thepipetting needle would not be possible.

The first sensor is preferably a Hall sensor. This has the advantagethat the position of the eccentrically rotating shaft can be detectedparticularly easily and reliably. In an advantageous embodiment, amagnet or a plurality of magnets is connected to the eccentricallyrotating shaft, and their magnetic field can be detected by the Hallsensor.

In another preferred embodiment, the vibration generator comprises atleast one motor. This has the advantage that the generation ofvibrations can be effected in an automated manner which is particularlysimple and cost-effective. The motor is preferably an electric motor.This has the advantage that the generation of vibrations can begenerated, regulated and monitored electronically in a particularly easymanner.

In another preferred embodiment, the vibration generator comprises aneccentric mechanism in which a motor, preferably an electric motor,drives an eccentric bearing and an eccentric ball bearing with aneccentrically rotating shaft.

In another advantageous embodiment, the first resetting elementcomprises at least one spring element, preferably a helical spring. Thishas the advantage that the first resetting element can have aparticularly simple and cost-effective configuration.

In a particularly preferred embodiment, the pipetting needle is movablewith the first connection element in the direction of the longitudinalaxis of the pipetting needle. This has the advantage that the pipettingneedle, if incorrectly placed in a vessel, for example, or on anassembly of the analyzer, can move correspondingly, and damage to thepipetting needle and/or to the item on which the pipetting needle isincorrectly placed can be avoided or at least limited.

A second sensor, preferably a microswitch or a Hall sensor, ispreferably provided which detects a movement of the pipetting needle inthe direction of the longitudinal axis of the pipetting needle relativeto the holder. This has the advantage that, if the pipetting needle isplaced incorrectly, the second sensor can trigger a signal and, forexample, the motor moving the pipetting needle in the direction of thelongitudinal axis of the pipetting needle can be switched off. Thus,damage to the pipetting needle and/or to the item on which the pipettingneedle is placed can be avoided or at least limited.

In another advantageous embodiment, the first securing element has atleast one grip, preferably at least two grips, for replacing thepipetting needle. This has the advantage that the pipetting needle canbe replaced particularly easily and comfortably by hand.

The pipetting needle is preferably heatable and/or coolable. This hasthe advantage, for example, that sample fluid or reagent fluid in thepipetting needle can be temperature-controlled and, for example, heatedor cooled to a defined temperature.

In an advantageous embodiment, the holder, the first connection element,the first securing element, the second connection element, the pipettingneedle, the suspension of the vibration generator and/or the handle orhandles, for example, comprise injection-molded plastics parts. This hasthe advantage that assembly and parts costs can be reduced.

Another subject of the invention is an analysis appliance whichcomprises an aforementioned pipetting device according to the invention.

A further subject of the invention is the use of a pipetting deviceaccording to the invention in an automatic analysis appliance.

Within the meaning of the invention, a “sample” is to be understood asthe material that is suspected to contain the substance to be detected(the analyte). The term “sample” comprises in particular biologicalliquids of humans or animals, e.g., blood, plasma, serum, sputum,exudate, bronchoalveolar lavage, lymph fluid, synovial fluid, seminalfluid, cervical mucus, feces, urine, cerebrospinal fluid, but also, forexample, tissue or cell culture samples that have been suitably preparedby homogenization or cell lysis for photometric determination,preferably nephelometric determination. Moreover, plant liquids ortissues, forensic samples, water and waste water samples, foods andpharmaceuticals, for example, can also serve as samples which, ifappropriate, are intended to undergo a corresponding preliminary sampletreatment step before the determination.

Quantitative detection involves measuring the amount, the concentrationor the activity of the analyte in the sample. The expression“quantitative detection” also covers semi-quantitative methods, whichcan detect only the approximate amount, concentration or activity of theanalyte in the sample or can serve only to provide a relative indicationof amount, concentration or activity. Qualitative detection is to beunderstood as the detection of the actual presence of the analyte in thesample, or the indication that the amount, concentration or activity ofthe analyte in the sample is below or above a defined threshold value orseveral defined threshold values.

BRIEF DESCRIPTION OF THE DRAWINGS

Persons skilled in the art will understand that the drawings, describedbelow, are for illustrative purposes only. The drawings are notnecessarily drawn to scale and are not intended to limit the scope ofthis disclosure in any way.

FIG. 1 shows a schematic view of the structure of the pipetting device(1) with a pipetting needle (2) inserted in the holder (5),

FIG. 2 shows a schematic view of the structure of the pipetting needle(2) and the first connection element (8),

FIG. 3 shows a schematic view of the structure of the holder (5) withvibration generator, without an inserted pipetting needle (2),

FIGS. 4, 7 and 8 show schematic views of details of the pipetting device(1) with a pipetting needle (2) inserted in the holder (5),

FIGS. 5 and 6 show schematic views of details of the pipetting device(1) during the insertion or removal of the pipetting needle by producingor releasing the connection between the holder (5) and the pipettingneedle (2).

Identical parts are provided with the same reference signs in all of thefigures.

DETAILED DESCRIPTION

The pipetting device (1) according to FIG. 1 is embedded in an analysisappliance (not shown) which is designed to perform a large number ofanalyses of samples. For this purpose, the automatic analysis appliancecomprises a large number of pipetting devices (not shown) and transportdevices (not shown) and also a control unit for automated evaluation ofthe analyses.

The pipetting device (1) comprises the movable device (4), which isdesigned as an automatically movable robot arm, the holder (5) with thevibration generator comprising the eccentric bearing (20), the motor(6), and also the pipetting needle (2). The pipetting needle (2)comprises a pipette inlet (18), a suspension (23) and a needle body (24)with a tip (7). The pipetting needle (2) is releasably connected to theholder (5) by means of the first securing element (10). The holder (5)is secured on the movable device (4). The first securing element (10) isdesigned as a blade and rests on a second securing element (11), whichis designed as a prism bearing. The first connection element (8)comprises a recess (21).

FIG. 2 shows the pipetting needle (2) with the tip (7), the needle body(24), the suspension (23) and the pipette inlet (18), and also the firstsecuring element (10), which is designed as a blade, and the firstconnection element (8). The first connection element (8) comprises therecess (21) and the first resetting element (9). The first securingelement (10) is mounted laterally on the suspension (23), in the upperpart of the latter. The direction of the longitudinal axis (3) of thepipetting needle (2) is indicated as a dot-and-dash line. Moreover, aclamping screw (22) is shown.

FIG. 3 shows the holder (5), which is mounted on the movable device (4)(not shown). The vibration generator comprises a motor (6), which drivesthe eccentric bearing (20) and the eccentric ball bearing (19) with theeccentrically rotating shaft (16), wherein the motor (6) is secured onthe holder (5). The holder (5) comprises two prism bearings (11), eachwith a second resetting element (12) (only partly visible) designed as aspring element, and the first sensor (14), which is designed as amicroswitch. Moreover, a magnet (17) is mounted laterally in the lowerarea of the eccentric bearing (20) in the direction of the eccentricball bearing (19).

FIG. 4 shows a detail of the pipetting device (1) with, inserted in theholder (5), a pipetting needle (2) with the pipette inlet (18), thesuspension (23), and a part of the needle body (24). The first securingelement (10) is designed as a blade, and the second securing element(11) is designed as a prism bearing. The first connection element (8),which is designed as an angle piece, comprises the recess (21) and islocated in the rest position and is not deflected downward from the restposition in direction A of the arrow toward the first resetting element(9). The releasable connection between the eccentric ball bearing (19)with the eccentrically rotating shaft (16) (not shown) of the shakingdevice and the first connection element (8) is produced, and there isdirect contact between the eccentric ball bearing (19) and the edge ofthe recess (21) in the first connection element (8). Moreover, theeccentric bearing (20) is shown. In the area of the prism bearing (11),a second sensor (14), which is designed as a microswitch, is mounted onthe holder (5). The microswitch triggers if the pipetting needle (2)sits incorrectly and the blades (10), which are secured laterally on thesuspension (23), are pressed out along the longitudinal axis (3) fromthe prism bearing (11).

FIG. 5 shows a detail of the pipetting needle (2) with pipette inlet(18), suspension (23), a part of the needle body (24) and also theholder (5), during the insertion of the pipetting needle (2) into theholder (5). The pipetting needle (2) is set obliquely and the blade ofthe first securing element (10) is located in spatial proximity to theprism bearing of the second securing element (11), although the blade isnot yet located in the prism bearing. The grips (15, 15′) in this casefacilitate the manual insertion (or also the removal) of the pipettingneedle (2) from the holder (5). The first connection element (8), whichis designed as an angle piece, is deflected downward from the restposition, in the direction A of the arrow, toward the first resettingelement (9). The releasable connection between the eccentric ballbearing (19) with the eccentrically rotating shaft (16) of the shakerdevice and of the first connection element (8) is released, and there isno direct contact between the shaft (16) and the first connectionelement (8). Moreover, the eccentric bearing (20) is shown. Theeccentric ball bearing (19) and the edge of the recess (21) in the firstconnection element (8) can be brought into releasable contact with eachother.

The parts shown in FIG. 5 are shown from a different angle in FIG. 6,except that the motor (6) of the shaker device is not shown. Moreover,FIG. 6 shows the first sensor (13), which is mounted on the holder (5)in spatial proximity to the eccentric drive (20) and eccentric ballbearing (19). The magnet (17) is mounted laterally in the direction ofthe eccentric ball bearing (19) in the lower area of the eccentricbearing (20), such that the magnet (17) interacts with the sensor (13),depending on the position of the eccentrically rotating shaft (16), andtherefore the position of the eccentrically rotating shaft (16) or theposition of the eccentric ball bearing (19) can be determined.

FIG. 7 shows a detail of the pipetting device (1) seen obliquely frombelow, with a pipetting needle (2) inserted into the holder (5), whereinthe pipette inlet (18) of the pipetting needle (2) and the suspension(23) are partly visible. The first connection element (8), which isdesigned as an angle piece, comprises the recess (21) and is located inthe rest position. The releasable connection between the eccentric ballbearing (19) with the eccentrically rotating shaft (16) of the vibrationgenerator and the first connection element (8) is produced, and there isdirect contact between the eccentric ball bearing (19) and the edge ofthe recess (21) in the first connection element (8). The eccentricbearing (20) is also shown.

FIG. 8 shows a detail of the pipetting needle (2) and of the holder (5),with the pipetting needle (2) inserted in the holder (5), with two grips(15, 15′) and with the first connection element (8). The blade of thefirst securing element (10) is located in the prism bearing of thesecond securing element (11). The second resetting element (12), whichis designed as a spring element, exerts a restoring force and holds theblade in the prism bearing.

LIST OF REFERENCE SIGNS

-   -   1 pipetting device    -   2 pipetting needle    -   3 longitudinal axis    -   4 movable device    -   5 holder    -   6 motor    -   7 tip    -   8 first connection element    -   9 first resetting element    -   10 first securing element    -   11 second securing element    -   12 second resetting element    -   13 first sensor    -   14 second sensor    -   15,15′ grip    -   16 shaft    -   17 magnet    -   18 pipette inlet    -   19 eccentric ball bearing    -   20 eccentric bearing    -   21 recess    -   22 clamping screw    -   23 suspension    -   24 needle body    -   A direction

What is claimed is:
 1. A pipetting device for an automatic analysisappliance, the pipetting device comprising: a pipetting needle with alongitudinal axis for the pipetting of liquids, the pipetting needlehaving a tip, a movable device that is movable in the direction of thelongitudinal axis of the pipetting needle and in at least one directionperpendicular to the direction of the longitudinal axis of the pipettingneedle and that is used for moving the pipetting needle within at leastone range of movement, a holder for the pipetting needle, wherein theholder is mounted on the movable device and to which the pipettingneedle is releasably connected, and a vibration generator that can setat least the tip of the pipetting needle in vibration, wherein thevibration generator is mounted on the movable device or on the holderand is configured to set at least the tip of the pipetting needle invibration during a transfer of the pipetting needle by the movabledevice from a first position to a second position in the at least onedirection perpendicular to the direction of the longitudinal axis. 2.The pipetting device as claimed in claim 1, wherein the pipetting devicecomprises a movable first connection element with a first resettingelement, and the first connection element produces a releasableconnection between the pipetting needle and the vibration generator. 3.The pipetting device as claimed in claim 2, wherein the first connectionelement has a shape of an angle piece.
 4. The pipetting device asclaimed in claim 1, wherein the pipetting device has a first and asecond securing element, the pipetting needle comprises a suspension,the first securing element is mounted laterally on the suspension andcomprises a blade, and the second securing element is mounted on theholder and comprises a prism bearing.
 5. The pipetting device as claimedin claim 4, wherein the pipetting device comprises a second resettingelement, and wherein the second resetting element fixes the blade andthe prism bearing in a stable position and releasably connects them. 6.The pipetting device as claimed in claim 2, wherein the vibrationgenerator comprises an eccentrically rotating shaft that can engage inthe first connection element.
 7. The pipetting device as claimed inclaim 6, further comprising a first sensor that detects the position ofthe eccentrically rotating shaft.
 8. The pipetting device as claimed inclaim 1, wherein the vibration generator comprises at least one motor.9. The pipetting device as claimed in claim 2, wherein the firstresetting element comprises at least one spring element.
 10. Thepipetting device as claimed in claim 2, wherein the pipetting needle ismovable with the first connection element in the direction of thelongitudinal axis of the pipetting needle.
 11. The pipetting device asclaimed in claim 1, further comprising a second sensor that detects amovement of the pipetting needle in the direction of the longitudinalaxis of the pipetting needle.
 12. The pipetting device as claimed inclaim 4, wherein the first securing element has at least one grip forreplacing the pipetting needle.
 13. The pipetting device as claimed inclaim 1, wherein the pipetting needle is heatable.
 14. An automaticanalysis appliance comprising a pipetting device as claimed in claim 1and a control unit for automated evaluation of analyses performed by theautomatic analysis appliance.
 15. A method of using a pipetting deviceas claimed in claim 1 in an automatic analysis appliance, the methodcomprising: transferring the pipetting needle with the movable devicefrom the first position to the second position; and vibrating at leastthe tip of the pipetting needle during the transferring.
 16. Thepipetting device as claimed in claim 5 wherein the second resettingelement comprises a spring element or a leaf spring.
 17. The pipettingdevice as claimed in claim 7 wherein the first sensor comprises a Hallsensor.
 18. The pipetting device as claimed in claim 8, wherein the atleast one motor comprises an electric motor.
 19. The pipetting device asclaimed in claim 9, wherein the at least one spring element comprises ahelical spring.
 20. The pipetting device as claimed in claim 11, whereinthe second sensor comprises a microswitch or a Hall sensor.